To augment natural healing processes of the knee menisci, tissue engineering creates new tissues via the[unreadable] combination of cells with biodegradable scaffolds. Under optimal conditions, a scaffold for tissue[unreadable] engineering would guide tissue regeneration as well as provide mechanical support during the healing[unreadable] process. Using an electrospinning process, random, non-aligned, nanofibrous scaffolds may be created[unreadable] from a variety of polymers. These meshes have fiber diameters similar to that of the native extracellular[unreadable] matrix (ECM) and support the attachment and growth of a number of cell types. This process may be further[unreadable] modified to create scaffolds possessing a defined fiber alignment; thereby producing a multidimensional[unreadable] nanofibrous micro-pattern for directed tissue growth. Such scaffolds possess both controllable and[unreadable] anisotropic mechanical properties and can direct cellular morphology. The overall objective of this proposal[unreadable] is to use rational design principles that incorporate the structure-function relationships of the meniscus to[unreadable] improve upon natural repair processes. Specifically, we suggest the application of a novel fiber-aligned[unreadable] nanofibrous biodegradable scaffold for use in meniscus tissue engineering and propose the following:[unreadable] Hypothesis 1: Compared to non-aligned constructs, fiber-aligned biodegradable nanofibrous meshes[unreadable] seeded with meniscus fibrochondrocytes (MFCs) or mesenchymal stem cells (MSCs) will maintain their[unreadable] anisotropic mechanical properties during tissue maturation and newly deposited ECM will align with the fiber[unreadable] direction. These aligned meshes will enhance the expression and deposition of fibrocartilaginous ECM[unreadable] molecules (type I and II collagen) and the resulting tensile properties of these constructs will be greater than[unreadable] that achieved by cells grown on non-aligned meshes, even after the polymeric component has degraded.[unreadable] Hypothesis 2: As a new matrix is deposited between the native tissue and the scaffold, the strength of the[unreadable] engineered interface will increase. The interface will be stronger when utilizing scaffolds aligned with the[unreadable] native tissue fiber direction, with interracial ECM deposited parallel to native fibers. As the meniscus is[unreadable] hypocellular, prior seeding of meshes with MFCs or MSCs will expedite interface formation. Pre-culture of[unreadable] cell-laden scaffolds prior to forming meniscus-scaffold composites will further expedite interface formation.[unreadable] These studies will validate the hypothesis that novel fiber-aligned biodegradable meshes will enhance the[unreadable] quality of engineered meniscal tissue by dictating anisotropy in the forming matrix. This work will also[unreadable] demonstrate the enhancement of scaffold integration to native tissue via pre-culture of fibrocartilaginous cells[unreadable] on an aligned scaffold. Finally, these studies will define parameters for further explorations of mechanical[unreadable] preconditioning of constructs, will lay the groundwork for in vivo animal studies, and will ultimately lead to the[unreadable] clinical application of new repair strategies to restore function in patients with meniscal tears.[unreadable]